Physical biochemical studies of a single-stranded nucleic acid binding protein termed Al were conducted. The protein binds cooperatively to either RNA or DNA and the full length protein binds much tighter than a truncated Al protein lacking the glycine- rich COOH-terminal domain (residues 185-319). Our studies suggest the mechanism of Al binding is similar to that of two well prokaryotic ssDNA binding proteins in that binding involves close approach of aromatic amino acids with nucleotide bases. We found that both the NH2-terminal and COOH-terminal domains make significant contributions to the overall free energy of binding of A1 to nucleic acids.